Immuno - Protection Against herpes simplex type II infection by Eleutherococcus extract

Key words Adaptogen; Elagen; Eleutherococcus senticosus; Herpes simplex; immunomodulator; standardisation.

Introduction

Eleutherococcus senticosus preparations have a long traditional history of use in Eastern Siberia and the surrounding territories where the plants originate. Belonging to the botanical family of Araliaceae, Eleutherococcus is used for the non-specific enhancement of resistance in humans and animals.

There are well over 1,500 papers on the chemistry and pharmocokinetics of the active ingredients; the biochemical, physiological and notably immunological effects which the extract has upon animals and human beings; and the observed clinical effects (1).

Most of this extensive literature is in Russian and it is only comparatively recently that it has become more accessible to international scientists and clinicians.

Eleutherococcus is already quite well known in Germany where a nucleus of pharmacological and some clinical data has largely originated from Prof. H. Wagner and his colleagues in the Pharmacological Department of Munich University (2).

Vast studies involving over 1200 people at the Volga Automobile Plant in the former USSR over a three-year period (1973 to 1975) reported an overall decrease by more than 30 per cent in the incidence of common viral infections such as colds and influenza (3).

A seven year study (1973 -1979) with truck drivers showed an over90 per cent decrease in the incidence of influenza over the total period (4).
Research work done with healthy volunteers by Bohn et al in Germany (1987) (5) which examined the effects of Eleutherococcus extract on the cellular immune status, showed a drastic increase in the absolute numbers of immunocompetent cells with an especially pronounced effect on T Lymphocytes, predominantly of the Helper/Inducer type as well as on Cytotoxic and Natural killer cells.
Substances which have a pharmacological ability to non specifically regulate the biochemical and physiological bodily processes towards normal regardless of the direction of any imbalances (i.e. downregulating for over-active states and upregulating for underactive state) without causing any disturbance or harm to the organisms are classified as "adaptogens" (6).

Eleutherococcus is believed to be one of the most efficient adaptogens to have been discovered so far in that it fulfils this criteria better than others in its class such as Schizandra chinensis and Panax ginseng. Eleutherococcus is particularly used for its immunomodulatory effects, i.e. its adaptogenic ability to modulateor regulate the immune system, and is particularly noted in Russia for its immune strengthening effects, especially in times of adversity and as such is commonly used in Russia as a support to the immune system during oncology treatments such as radiotherapy and chemotherapy (7).

It takes three months of continuous usage of Eleutherococcus for its full potential to be reached which is one of the reasons that the trial was done over a six-month period. Elagen (d) is a pure standardised extract of Eleutherococcus senticosus which does not contain any additives or and other active substances.

Elagen (d) is registered as a prescription-free food supplement or tonic in the UK and Germany. Elagen (d) is standardised against the principle active ingredients - glycosides, Eleutherosides B and E.

Biochemical formulae: Eleutheroside B Eleutheroside E Glycoside of syringine Di-B-D glycoside of syringaresinol (dimer of Eleutheroside B)

As a standardised extract Elagen (d) unlike other available Eleutherococcus products contains known and consistent quantities of these Eleutherosides in the recommended ratio and is thus ideally suited to research purposes. Elagen (d) is the only encapsulated standardised extract of Eleutherococcus senticosus available in the UK.

Method

Ninety-three volunteers from the Herpes Association took part in the trial (52 men and 41 women) and were randomly assigned to verum or placebo groups. The placebo capsules were opaque capsules containing inert stoneground rice flour with the verum capsules appearing identical but containing 2 grams equivalent of whole dried Eleutherococcus senticosus root in a base of stoneground rice flour (Elagen (d) high potency capsules containing 2000mg HPLC standardised extract.) The trial was double blind with neither those taking part or those supplyingthe capsules knowing which were received, the code was kept confidentially by an independent third party until after the trial was completed.

Volunteers were sent a preliminary questionnaire asking for the severity, duration and frequency of Herpes simplex symptoms six months prior to the start of the trial together with a calendar on which to mark any recurrent symptoms experienced on a daily basis during the trial. The trial took place over a six-month concurrent period. At the end of the six months period, a further questionnaire was sent to establish the perceived effects from taking the trial capsules.

The results were statistically analysed by an independent party. The statistical significance of the results was evaluated using standard t-tests applied to the two groups of volunteers, using two-tail unpaired t values. All the results analysed were statistically significant between 0.0002 and 0.0007 error probability for the verum (Elagen) effects calculated for two groups using independent normal distributions. Results were analysed for all the sorted answers to the question (i.e. did the trial capsules help? Did they affect severity, duration, and frequency?)

Results

Those in the verum group taking Eleutherococcus senticosus extract (Elagen) had shorter, fewer and less severe outbreaks. Many of them reported no recurrences at all. Those in the placebo group mainly reported little or no change. Eleutherococcus takes three months to build up to full efficacy both as a general adaptogen and as an immunomodulator. This slow build up effect was noticeable on the calendars which were returned - two thirds of the outbreaks which volunteers in the verum group had reported occurred within the first three months and only one third in the second three months.

One particularly interesting result came from a couple who both took part; the one in the verum group reported an improvement and the one in the placebo group reported no change.

Compliance was good for a voluntary trial of this kind, which relied on the good will of the participants. Only two men and six women did not return their questionnaires despite reminders. Interestingly, the majority of the six who did not reply to the questionnaires were from the placebo group. Results were statistically significant at p-0.0002 to 0.0007 for the verum group taking Eleutherococcus for the overall benefit, help with severity, help with duration and help with frequency (table 1).

(Table 1) Combining the results for men & women based on the final quesionnare

	Verum (44)					Placebo (41)
Overall did it help you?	YES 33    NO 11					YES 14    NO 27
	Best to worst (4=no change)					Best to worst (4=no change)
Did the trial capsules help?	1	2	3	4	5	1	2	3	4	5
	12	10	11	10	1	2	5	10	23	0
Did they help with the severity of Herpes Simplex outbrealk?	1	2	3	4	5	1	2	3	4	5
	10	14	8	10	2	1	7	10	22	1
Did they help with specific symptoms such as itching burning, pain?	YES 19    NO 23					YES 6    NO 34
Would you continue with these capsules?	YES 20    NO 22					YES 13    NO 28
Any side effects?	YES 20    NO 41					YES 4    NO 17

 

Notes:
1. One did not answer this question.
2. One put "not sure". Reasons given for not wanting to continue: Two men experienced side effects, one man said he felt that his outbreaks were worse. The two who had benefited said: "I've benefited psychologically; now I don't need them; and "I don't like taking things". The other seven men had only slight improvement or none at all.
3. One put not sure
4. One put " I didn't have any recurrences to be helped." One put "Not sure. I've had some prodromal symptoms but no outbreaks."
5. One put not sure, Apart from five women to whom Elagen was of no help, others said, "I've stopped having outbreaks." "I don't like swallowing the capsules" and two said that it only made a minimum improvement to the frequency of the outbreaks.

These results are also representative of results for the questions regarding severity, duration and frequency which have similar numerical results and give similar graphs on tabulation.

On the women's calendars for the six months before the trial began there were an average of 4.46 recurrences lasting an average of 6.75 days each. During the trial, women in the verum group had an average of 2.05 outbreaks lasting 4.98 days, women in the placebo group had 3.91 recurrences lasting 5.42 days.

For the men, the average number of recurrences in the six months prior to the trial was 4.85 lasting an average of 7.08 days each. During the trial men in the verum group had an average of 2.13 outbreaks lasting 4.19 days, men on the placebo had 3.79 outbreaks lasting 5.64 days.

Tables to show the average numbers of recurrent outbreaks of Herpes simplex against the average duration of the recurrences in days plotted separately from men and women. This shows a significant difference in both groups between those taking Elagen in the verum group as opposed to the results prior to the trial allowing for the placebo effect. Surface area under the graph is equivalent to the amount of time (days) during which recurrences were experienced over a six month period. This is significantly reduced for the group taking Elagen.

No side effects were reported in the group of women taking either verum or placebo capsules. However, six men reported minor side effects of which four occurred in the placebo group (runny nose, headaches) and two in the verum group (tiredness, acid stomach, and heavy headedness). These were not thought to be significant findings.

The comments made by some of the volunteers are relevant and add weight to the results in that those for the verum group were very much more positive than for the placebo group although there was a very definite placebo effect. Some of these comments are listed.

For the verum group these included:

• "Good"
• " Definitely helped"
• " It cleared my spots too"
• " I was fine on the capsules but have had frequent attacks since"
• " During a particularly stressful time, my outbreaks usually become more severe. It was a stressful time when I was taking this drug but the outbreaks were the least severe that I have ever experienced and cleared up particularly quickly."
• " Taking the capsules improved my whole life Ébut since stopping the capsules my outbreaks have been very frequent."
• " If I was on Elagen capsules they were marvellous - particularly as I was experiencing different forms of stress."
• " I felt several times that I was gong to develop a sore but it never actually developed."

Some of the comments from those on the placebo were also quite positive. The results suggest quite strongly that Eleutherococcus senticosus does have a protective effect against recurrences of the herpes simplex type II virus infection and it would be interesting to proceed with a larger trial with greater numbers of herpes patients not only looking at the duration, frequency and severity of attacks (perhaps over a longer period such as 12 months) but to see if there is any correlation between the previously reported immunomodulating effects of Eleutherococcus senticosus and its observed anti viral effects by observing the t cell populations.

It would be useful to determine whether these results are applicable to the reduction of Herpes Simplex Type 1 recurrences. The manner in which Eleutherococcus exerts its actions on the human immune system remains unclear but perhaps with further in-depth research this activity could be elucidated and amplified in order to enhance greater immunity against viruses. Work in Russia at the Institute of Phytopharmacy is already advancing in the discovery of a phytosome specific to Eleutherococcus, which amplifies the adaptogenic and immunomodulating effects of Eleutherococcus. Plant extracts such as Eleutherococcus should not be ignored as they can have very beneficial demonstrable effects and it is time that greater note were taken of their potential value in medicine today. If a strongly immuno protective-substance could be identified or developed from existing adaptogens such as Eleutherococcus, then this would have wide reaching implications for many conditions including prevention of infection in immunocompromised patients.

Discussion

The results suggest quite strongly that Eleutherococcus senticosus does have a protective effect against recurrences of the herpes simplex type II virus infection and it would be interesting to proceed with a larger trial with greater numbers of herpes patients not only looking at the duration, frequency and severity of attacks (perhaps over a longer period such as 12 months) but to see if there is any correlation between the previously reported immunomodulating effects of Eleutherococcus senticosus and its observed anti viral effects by observing the t cell populations. It would be useful to determine whether these results are applicable to the reduction of Herpes Simplex Type 1 recurrences.

The manner in which Eleutherococcus exerts its actions on the human immune system remains unclear but perhaps with further in-depth research this activity could be elucidated and amplified in order to enhance greater immunity against viruses. Work in Russia at the Institute of Phytopharmacy is already advancing in the discovery of a phytosome specific to Eleutherococcus, which amplifies the adaptogenic and immunomodulating effects of Eleutherococcus.

Plant extracts such as Eleutherococcus should not be ignored as they can have very beneficial demonstrable effects and it is time that greater note were taken of their potential value in medicine today. If a strongly immuno protective-substance could be identified or developed from existing adaptogens such as Eleutherococcus, then this would have wide reaching implications for many conditions including prevention of infection in immunocompromised patients.

References:

1. Farnsworth N et al Eleutherococcus senticosus; current status as an Adaptogen. Economic and Medicinal Plant Research Vol 1 Academic PressInc. London 1983.
2. Von Sabine Bladt and Hildebert Wagner, Munchen and W.S Woo,Seoul .DC and HPLC Analysis of Eleutherococcu-bzw Acanthopanax - Extraction and Companion of Phytoprep. Deutsche Apotheker Zeitung 130 Jan 27 (1499-1509) 1990.
3. Galanova, 1, K (1977). Eleutherococcus in the prophylaxis of influenza, and relapses of essential hypertension in Adaption and Adaptogens. The Far Eastern Research Centre USSR Academy of Science, Vladivostock 126 -127.
4. Shchezin, A K et all (1981). Eleutherococcus in the prophylaxis of influenza, essential hypertension and Ischaemic Heart Disease in the drugs of the VAP New Data on Eleutherococcus and other adaptogens.
5. Bohn B C T Nebe, C Birr. Flow Cytometric Studies with ES extract as an Immunomodulatory Agent. (Drug Res.) 37 (11) No 10 (1987).
6. Brekhman II. Man and Biologically Active Substances. Pergamon Press, Oxford (1980) 7. Kupin V. Eleutherococcus and other Biologically Active Modifiers in Oncology, Medesport, Moscow 1985.